Moore, Biochem. Biophys. Res. Commun., 159 420 (1989) discloses peptidyl inhibitors of HIV protease. Erickson, European Patent Application No. WO 89/10752 discloses derivatives of peptides which are inhibitors of HIV protease.
U.S. Pat. No. 4,652,552 discloses methyl ketone derivatives of tetrapeptides as inhibitors of viral proteases. U.S. Pat. No. 4,644,055 discloses halomethyl derivatives of peptides as inhibitors of viral proteases. European Patent Application No. WO 87/07836 discloses L-glutamic acid gamma-monohydroxamate as an antiviral agent.
Jadhav et al., Bioorganic & Med. Chem. Lett 2(4) 353-356 (1992), and Dreyer et al., Biochemistry 32 (3) 937-47 (1993), disclose symmetric linear HIV-1 protease inhibitors which contain an acetonide protecting group.
Jadhav et al., U.S. Pat. No. 5,294,720 discloses the preparation of linear unprotected or acetonide protected diaminodihydroxyalkanes and amino acid and peptide derivatives thereof as retroviral protease inhibitors.
Jadhav et al., Bioorganic & Med. Chem. Lett 2(4) 353-356 (1992), and Chenera et al., Bioorg. Med. Chem. Lett. 1(4) 219-22 (1991), disclose the synthesis of C2-symmetric and pseudosymmetric HIV-1 protease inhibitors from D-mannitol and D-arabitol.
European Patent Application No. EP 486948 discloses linear diaminohydroxy compounds useful as HIV-1 protease inhibitors.
European Patent Application No. EP 501568-A1 discloses cyclic sulfamide compounds useful as 5-HT1 receptor agonists.
Lam et al., PCT International Publication Number WO 93/07,128 discloses cyclic carbonyl compounds and derivatives thereof which are useful as human immunodeficiency virus (HIV) protease inhibitors for the treatment of HIV infection. The compounds disclosed in WO 93/07128 include cyclic HIV protease inhibitor compounds of the formula below where W may be --N(R.sup.22)C(.dbd.O)N(R.sup.23)-- or --N(R.sup.22)S(.dbd.O)N(R.sup.23)--. ##STR1##
Copending commonly assigned U.S. patent applications Ser. No. 08/197,630 filed Feb. 16, 1994, Ser. No. 08/047,330, filed Apr. 15, 1993, and Ser. No. 08/023,439, filed Feb. 26, 1993, disclose cyclic HIV protease inhibitors, including cyclic sulfamide HIV protease inhibitors, of the formula below wherein W may be --N(R.sup.22)S(.dbd.O).sub.2 N(R.sup.23)--. ##STR2##
As disclosed in the above copending commonly assigned patent applications, such cyclic sulfamide compounds, which may be made using the processes of the present invention, are non-peptidic, low molecular weight, orally bioavailable compounds useful as inhibitors of HIV protease and for the treatment of HIV infection. The HIV protease inhibitory activity of the cyclic sulfamide can be increased by two to three orders of magnitude by alkylating one or both of the urea nitrogens.
Consequently, a need exists for more efficient and cost-effective methods for the preparation of the cyclic sulfamide HIV protease inhibitor compounds of the above copending commonly assigned patent applications in high yields from readily available starting materials. The present invention provides improved processes for the synthesis of such cyclic sulfamide HIV protease inhibitor compounds.